Absence of genotoxic impact assessed by micronucleus frequency in circulating lymphocytes of workers exposed to cadmium.

PURPOSE: Cd is considered as a genotoxic carcinogen for which a threshold can be identified. This threshold has, however, not been established and the shape of the relationship between Cd exposure and genotoxic effects is unknown. The aim of the present study was to analyse the shape of the dose-response relationship for the genotoxic effects of Cd in occupational settings. METHODS: The study has a cross-sectional design and includes 60 healthy male and female workers with known Cd exposure selected from two plants manufacturing or recycling nickel-Cd batteries. The frequency of MN was measured in circulating lymphocytes, and related to internal Cd doses (Cd-B, Cd-U). Determinants of MN frequency were traced by multivariate regression analysis. RESULTS: Cd exposure covered a wide range as measured by Cd-B (0.02-1.26 µg/dL), Cd-U (0.26-15.80 µg/g creat) and seniority in the plant (1-42 years). Gender was the only parameter significantly associated with MN frequency, women having on average 8.5 additional MN/1000 BN cells compared to men. Cd-B, Cd-U or Ni-U did not influence MN frequency when adjusted for gender and other potential confounders. CONCLUSION: This finding is consistent with the existing knowledge on the mechanisms governing the genotoxic activity of Cd, which are all non-stochastic and thresholded. The threshold for systemic genotoxic effects of Cd is thus beyond the range of internal exposure considered in the present investigation.

Cobalt and its compounds: update on genotoxic and carcinogenic activities.

This article summarizes recent experimental and epidemiological data on the genotoxic and carcinogenic activities of cobalt compounds. Emphasis is on the respiratory system, but endogenous exposure from Co-containing alloys used in endoprostheses, and limited data on nanomaterials and oral exposures are also considered. Two groups of cobalt compounds are differentiated on the basis of their mechanisms of toxicity: (1) those essentially involving the solubilization of Co(II) ions, and (2) metallic materials for which both surface corrosion and release of Co(II) ions act in concert. For both groups, identified genotoxic and carcinogenic mechanisms are non-stochastic and thus expected to exhibit a threshold. Cobalt compounds should, therefore, be considered as genotoxic carcinogens with a practical threshold. Accumulating evidence indicates that chronic inhalation of cobalt compounds can induce respiratory tumors locally. No evidence of systemic carcinogenicity upon inhalation, oral or endogenous exposure is available. The scarce data available for Co-based nanosized materials does not allow deriving a specific mode of action or assessment for these species.

Carcinogenic potential of formaldehyde in occupational settings: a critical assessment and possible impact on occupational exposure levels.

OBJECTIVES: To review epidemiological studies which led to a change in the classification of formaldehyde by the International Agency for Research on Cancer (IARC) in 2004 as well as studies published thereafter, with the objective to examine whether occupational exposure levels for formaldehyde should be adapted. METHOD: Cohort and case-control studies investigating the association between occupational exposure to formaldehyde and nasopharyngeal cancer (NPC) and reporting estimates of formaldehyde exposure as well as the most recent meta-analyses, published after 1994, were reviewed. RESULTS: Evidence of an association between occupational formaldehyde exposure and NPC appears debatable. Results of the cohort studied by Hauptmann et al. (Am J Epidemiol 159(12):1117-1130, 2004) were key findings in the IARC evaluation. In this study, mortality from NPC was elevated compared with that of the US general population. However, internal comparison analysis using alternative categorization revealed that none of the relative risk for NPC was statistically significantly increased in any category of exposure (Marsh and Youk in Regul Toxicol Pharmacol 42(3):275-283, 2005) and re-analyses of the data highlighted the inappropriateness of the exposure assessment used by Hauptmann et al. (Am J Epidemiol 159(12):1117-1130, 2004) and Marsh et al. (Regul Toxicol Pharmacol 47(1):59-67, 2007). Two other cohorts (Coggon et al. in J Natl Cancer Inst 95(21):1608-1615, 2003; Pinkerton et al. in Occup Environ Med 61(3)193-200, 2004) reported no increase in NPC. Two case-control studies brought some evidence of an increased risk of NPC but the assessment of exposure levels was uncertain. DISCUSSION: Human studies fail to raise a convincing conclusion concerning the carcinogenicity of formaldehyde and are not helpful to delineate a possible dose-response relationship. Experimental data indicate that in rats, the carcinogenic activity of formaldehyde is associated with cytotoxic/proliferative mechanisms. Therefore protecting from these effects associated with formaldehyde exposure should be sufficient to protect from its potential carcinogenic effects, if any in humans. CONCLUSION: Current occupational exposure levels to formaldehyde, set to protect against local irritation, should not be adapted.

A semi-active milling procedure in view of preparing implantation beds in robot-assisted orthopaedic surgery.

Bone cutting in total joint reconstructions requires a high accuracy to obtain a well-functioning and long-lasting prosthesis. Hence robot assistance can be useful to increase the precision of the surgical actions. A drawback of current robot systems is that they autonomously machine the bone, in that way ignoring the surgeon's experience and introducing a safety risk. This paper presents a semi-active milling procedure to overcome that drawback. In this procedure the surgeon controls robot motion by exerting forces on a force-controlled lever that is attached to the robot end effector. Meanwhile the robot constrains tool motion to the planned motion and generates a tool feed determined by the feed force that the surgeon executes. As a case study the presented milling procedure has been implemented on a laboratory set-up for robot-assisted preparation of the acetabulum in total hip arthroplasty. Two machining methods have been considered. In the first method the surgeon determines both milling trajectory and feed by the forces that he/she executes on the force-controlled lever. In the second method the cavity is machined contour by contour, and the surgeon only provides the feed. Machining experiments have shown that the first method results in large surface irregularities and is not useful. The second method, however, results in accurate cavity preparation and has therefore potential to be implemented in future robot systems.

Prostate cancer among pesticide applicators: a meta-analysis.

OBJECTIVES: To analyse data from peer-reviewed, case-referent and cohort studies, studying the occurrence of prostate cancer in pesticide applicators and in some other, related, occupational categories, in order to determine a possible relationship of cancer of the prostate with pesticide exposure; to calculate a meta-rate ratio and to compare it with the meta-rate ratios obtained in a previous meta-analysis performed over a shorter time (1995-2001) in a broader exposure category, including many pesticide-related agricultural and non-agricultural occupations. METHODS: Medline was searched for the years between 1966 and 2003, and relevant studies were identified from 1986 on. We conducted a meta-analysis of 22 studies complying with the inclusion criteria in order to pool their relative risk (RR) estimates. Studies were summarised and assessed for homogeneity and publication bias. RESULTS: The meta-rate ratio, based on 22 estimates of RR, is 1.24 [95% confidence interval (95% CI) 1.06-1.45]. This pooled risk estimate for the occupational categories selected is higher than the one previously calculated for farmers in general over a shorter period of publication. Substantial heterogeneity of rate ratios exists between the different studies. The major source of heterogeneity identified is geographic location. Increased meta-rate ratios are observed for studies derived from North America as well as from Europe, the meta-rate ratios from Europe being lower than those from North America. There is no obvious indication of publication bias. CONCLUSION: The increased meta-rate ratio for prostate cancer in agricultural pesticide applications provides additional evidence for a possible relationship between pesticide exposure and prostate cancer. The homogeneity observed between the individual rate ratios, after we had regrouped the data according to geographic location, tends to increase the consistency of the association. However, the data available from the individual studies do not provide sufficient exposure information for firm conclusions to be drawn about pesticide exposure as the cause of prostate cancer, independently from other factors.

Occupation related pesticide exposure and cancer of the prostate: a meta-analysis.

AIMS: To summarise recent literature on the risk of prostate cancer in pesticide related occupations, to calculate the meta-rate ratio, and to compare it to data from meta-analyses previously published. METHODS: A meta-analysis of 22 epidemiological studies, published between 1995 and 2001, was conducted in order to pool their rate ratio estimates. Studies were summarised and evaluated for homogeneity and publication bias. RESULTS: The meta-rate ratio estimate, based on 25 estimators of relative risk from 22 studies, was 1.13 (95% CI 1.04 to 1.22). Significant heterogeneity of rate ratios existed among the different studies. Therefore, a stratified analysis was carried out. Major sources of heterogeneity identified were geographic location, study design, and healthy worker effect. Overall, pooled risk estimates for studies derived from Europe were lower than those derived from the USA/Canada. A significant increase in rate ratio was observed for the occupation category of pesticide applicators, whereas no significant increase was observed for farmers. There was no evidence of publication bias. CONCLUSION: This increased meta-rate ratio for prostate cancer in different pesticide related occupations, including farmers, is very similar to three, previously published, meta-rate ratios for prostate cancer in farmers calculated from studies published before 1995. Although the underlying data do not identify pesticide exposure as an independent cause for prostate cancer, the fact that an increased meta-rate ratio is again obtained points to occupational exposure to pesticides as a possible factor. Future epidemiological studies should focus, as far as possible, on reliable methods to estimate actual exposure.

Performance of a submerged aerated filter and a rotating biological contactor under dynamic loading conditions.

Two types of small wastewater treatment systems were studied for their performance under normal conditions, including the hydraulic peak flows associated with small systems connected to just one house. Furthermore, the systems were subjected to a 7-day starvation period to simulate the effect of a holiday from home. The systems studied are (1) a combined submerged aerated filter-activated sludge system and (2) a rotating biological contactor system. Both the organic removal and the nitrification process were closely monitored. During normal operation, very good treatment results were achieved. The combined SAF-AS system realized 95% BOD removal, 88% COD removal and 94% NH4-N removal. The RBC system removed 92% of the BOD, 89% of the COD and 99% of the ammonium nitrogen. Both systems do not experience severe problems dealing with the lack of influent for a duration of seven days. The effluent concentrations did not change much, except for a small peak of nitrite which was present in all tests. However, both the ammonium oxidizing and the nitrite oxidizing bacterial populations were still active, as evidenced by the continued removal of ammonium and formation of nitrate.

Genes and orthopedics: from gene to clinic and vice versa.

Recent advances in molecular biology have greatly helped in understanding the mechanisms involved in normal skeletal morphogenesis. Multiple genes involved in normal skeletal development have been identified, but several others still await discovery. Mutations in these genes are often responsible for the congenital skeletal malformations that we see in the orthopedic clinics. In this overview we would like to emphasize the importance of the interaction between orthopaedic surgeons, molecular biologists and geneticists.

Hieronymus Bosch (1450-1516): paleopathology of the medieval disabled and its relation to the Bone and Joint Decade 2000-2010.

BACKGROUND: At the start of the Bone and Joint Decade 2000-2010, a paleopathologic study of the physically disabled may yield information and insight on the prevalence of crippling disorders and attitudes towards the afflicted in the past compared to today. OBJECTIVE: To analyze "The procession of the Cripples," a representative drawing of 31 disabled individuals by Hieronymus Bosch in 1500. METHODS: Three specialists--a rheumatologist, an orthopedic surgeon and a neurologist--analyzed each case by problem-solving means and clinical reasoning in order to formulate a consensus on the most likely diagnosis. RESULTS: This iconographic study of cripples in the sixteenth century reveals that the most common crippling disorder was not a neural form of leprosy, but rather that other disorders were also prevalent, such as congenital malformation, dry gangrene due to ergotism, post-traumatic amputations, infectious diseases (Pott's, syphilis), and even simulators. The drawings show characteristic coping patterns and different kinds of crutches and aids. CONCLUSION: A correct clinical diagnosis can be reached through the collaboration of a rheumatologist, an orthopedist and a neurologist. The Bone and Joint Decade Project, calling for attention and education with respect to musculoskeletal disorders, should reduce the impact and burden of crippling diseases worldwide through early clinical diagnosis and appropriate treatment.

Does functional treatment of idiopathic clubfoot reduce the indication for surgery? Call for a widely accepted rating system.

We present our experience of treatment by physiotherapy, continuous passive motion and strapping in a series of 100 clubfeet classified on a scale of severity according to Dimeglio. Twenty-five percent were good after conservative treatment, and 75% required an operation. There were no recurrences or additional procedures. Before the introduction of the functional treatment in our department, 100% required some sort of surgical intervention and 51% required an additional procedure. In comparison with the results published by Dimeglio et al., the greatest discordance is observed in grade 2 clubfeet.

Parsonage-Turner syndrome after total-hip arthroplasty.

A 68-year-old patient developed Parsonage-Turner syndrome after total hip arthroplasty. There was an acute onset of intense pain in the shoulder 48 hours after surgery followed by complete paralysis of the shoulder and almost complete loss of strength in the arm. Recovery was slow, and mild weakness persisted 7 years after the operation. Parsonage-Turner syndrome has been associated with various surgical procedures but has not been reported after total hip arthroplasty. For medicolegal reasons, it should be distinguished from a traction injury of the brachial plexus or compression of the radial or ulnar nerve resulting from positioning of the patient. Parsonage-Turner syndrome should be considered in the differential diagnosis when a patient describes pain or weakness in the shoulder after joint arthroplasty.

Chiari osteotomy in children and young adults.

From 1972 to 1991, 50 Chiari procedures were performed in 41 patients. The follow-up period ranged from 3 years to 24 years and 3 months, with an average of 7 years. Age of the patients at operation averaged 10 years and 6 months (3 years and 1 month to 28 years and 6 months). The best results were obtained in patients older than 10 years of age. There was no statistical relationship between the technical details of Chiari osteotomy (angle of Chiari, displacement and distance to the femoral head) and the results.

Single event multilevel botulinum toxin type A treatment and surgery: similarities and differences.

The present study attempts to provide objective evidence of two treatment options for children with cerebral palsy (CP): multilevel botulinum toxin type A (BTX-A) injections and multilevel surgery. The purpose of the study was to clarify the differences and the similarities, and common treatment principles of both treatment strategies. Objective three dimensional gait analysis data were studied retrospectively in two patient groups pre- and post-treatment (randomly selected from a group of children that were treated between 1998 and 1999). In the first group, 29 children with CP were managed with BTX-A injections according to an integrated multilevel approach (Molenaers et al., 1999a). A second group of 23 children with CP were managed by a more traditional single event multilevel surgery, also according to an integrated approach. Our aim was to evaluate the differences as well as the similarities between both patient groups, using a set of 56 parameters selected from three-dimensional gait analysis. The unifying concept between management with BTX-A injections and orthopaedic surgery was the adoption of a multilevel approach at one session. The groups demonstrated considerable differences with respect to age, pretreatment condition and amount and level of improvement after treatment. The children who received BTX-A were typically younger, and showed primary gait problems in the distal joints, whereas the children who underwent surgery demonstrated a higher frequency of gait deviations in the transverse plane and had more complications. Although the benefit of both treatments was confirmed by the present study, a difference in the amount and level of improvement was also demonstrated. In conclusion, these treatment modalities should be regarded as complementary rather than mutually exclusive treatments, with both calling for an integrated approach.

Kinematic and kinetic evaluation of the ankle after intramuscular injection of botulinum toxin A in children with cerebral palsy.

Intramuscular botulinum toxin A (BTA) injection has a role in the conservative management of dynamic equinus deformity in children with cerebral palsy. The effect of BTA injection of the gastrocsoleus muscle during gait was evaluated. Eight children with hemiplegia (median age 4.4 years, range 2 to 8 years) were included in this retrospective study. Assessment included kinematic and kinetic gait analysis before and after (median 57.5 days) treatment. Postinjective kinematics showed significant improvement of ankle range of motion in the stance phase of gait. Ankle kinetics demonstrated a significant decrease of pathological power generation in midstance. The ankle power quotient (APQ) was also significantly improved. Ankle power in terminal stance was improved, although not to a significant level. These results provide evidence of normalization of energy production at the ankle, which is critical for normal gait. The effect of BTA is temporary and can be successfully repeated. This allows deferring the need for surgical intervention until the child is older and recurrence rate is lower.

A young female with asymmetric manifestations of larsen syndrome: another example of unilateral somatic cell-line mosaicism.

Larsen syndrome is characterized by multiple congenital joint dislocations, typical skeletal defects and facial dysmorphism. In this article, we present a female patient with asymmetric Larsen syndrome. We hypothesise that the asymmetric distribution of clinical features in our patient is likely caused by post-zygotic somatic cell-line mosaicism of a dominant gene mutation.

Stress fracture of the inferior and superior pubic ramus in a man with anorexia nervosa and hypogonadism.

The authors present the case of a 23-year-old athlete with a bifocal stress fracture of the pubis. Bifocal cases are rather rare, therefore an insufficiency fracture was suspected. Further investigation showed osteopenia due to secondary hypogonadotropic hypogonadism caused by anorexia nervosa. This case illustrates the need for awareness of underlying metabolic disorders in very rare cases of stress fractures in athletes.

Physical map of a 1.5 mb region on 12p11.2 harbouring a synpolydactyly associated chromosomal breakpoint.

Synpolydactyly (SPD) is a rare malformation of the distal limbs known to be caused by mutations in HOXD13. We have previously described a complex form of SPD associated with synostoses in three members of a Belgian family, which co-segregates with a t(12;22)(p11.2;q13.3) chromosomal translocation. The chromosome 12 breakpoint of this translocation maps to 12p11.2 between markers D12S1034 and D12S1596. Here we show that a mutation in the HOXD13 gene is not responsible for the phenotype, and present a physical map of the region around the 12p11.2 breakpoint. Starting from D12S1034 and D12S1596, we have established a contig approximately 1.5 Mb in length, containing 13 YAC clones, 16 BAC clones, and 11 cosmid clones. FISH analysis shows that cosmid LL12NCO1-149H4 maps across the breakpoint, and Southern blot experiments using fragments of this cosmid as probes identify a rearranged BamHI fragment in the patients carrying the translocation. A search for expressed sequences within the contig have so far revealed one CpG island, seven anonymous ESTs and three previously characterised genes, DAD-R, KRAG and HT21, all of which were found not to be directly disrupted by the translocation. The gene represented by EST R72964 was found to be disrupted by the translocation. These findings lay the groundwork for further efforts to characterise a gene critical for normal distal limb development that is perturbed by this translocation.

Gait analysis in myelomeningocele: possibilities and applications.

Gait analysis with a fully integrated laboratory is a relatively new instrument in the armamentarium of the pediatric orthopedic surgeon. The introduction of it has been especially successful in neuromuscular pathology and, particularly, in cerebral palsy. In spina bifida, however, it also enhances substantially the possibilities of detailed analysis of the locomotion problem. It is, furthermore, a very useful instrument in evaluating treatment and in follow-up. With a few examples, this paper tries to show the possibilities and advantages of a gait laboratory in the evaluation of patients with ambulatory spina bifida.